Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets

Ersen Kavak, Ayaz Najafov, Nuri Ozturk, Tuncay Seker, Kader Cavusoglu, Tolga Aslan, Adil Doganay Duru, Tahsin Saygili, Gerta Hoxhaj, Mahmut Can Hiz, Durisehvar Ozer Unal, Necla Birgül-Iyison, Mehmet Ozturk, Ahmet Koman

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. β-catenin, a cytoplasmic component, plays a major role in the transduction of canonical Wnt signaling. The aim of this study was to identify novel genes that are regulated by active β-catenin/TCF signaling in hepatocellular carcinoma-derived Huh7 cells with high (transfected) and low β-catenin/TCF activities. High TCF activity Huh7 cells led to earlier and larger tumor formation when xenografted into nude mice. SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis were performed in parallel, to compare gene expression between low and high β-catenin/TCF activity clones, and also those that had been rescued from the xenograft tumors. SAGE and genome-wide microarray data were compared and contrasted. BRI3 and HSF2 were identified as novel targets of Wnt/β-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment.

Original languageEnglish (US)
Pages (from-to)1523-1535
Number of pages13
JournalCellular Signalling
Volume22
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • BRI3
  • HCC
  • HSF2
  • Wnt/TCF4/β-catenin targets
  • Xenograft

ASJC Scopus subject areas

  • Cell Biology

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